The present invention provides an efficient, safe and cost effective way to prepare 5-(4-methyl-1H-imidazol-1-yl)-3-(trifluoromethyl)-benzenamine of the following formula (I):

The compound of formula (I) is an intermediate for the preparation of substituted pyrimidinylaminobenzamides of formula (II):

Compounds of formula (II) have been disclosed in W. Breitenstein et al., WO 04/005281 A1, the disclosure of which is incorporated herein by reference. These compounds have been shown to inhibit one or more tyrosine kinases, such as c-Abl, Bcr-Abl, the receptor tyrosine kinases PDGF-R, Flt3, VEGF-R, EGF-R and c-Kit. As such, compounds of formula (II) can be used for the treatment of certain neoplastic diseases, such as leukemia.
Previous synthesis of compound (I) involves a 4 step synthetic route starting with an aromatic substitution reaction of compound (IIIa), 4-methyl-1H-imidazole, with compound (IV), which requires employing high energy (150° C.) (Scheme 1).

Furthermore, transformation of compound (VI) to compound (VII) via Curtius rearrangement utilizes an unsafe reagent, diphenylphosphorylazide. This reaction produces inconsistent product yields and quality. In addition, removing the resulting diphenylphosphoric acid by-product is difficult. The carbamate product (VII) needs to be purified by chromatography, which is expensive and time consuming for commercial operations.
It is an object of this invention to provide alternative processes to make the compound of formula (I) efficiently and in high yields.
It is a further object of this invention to make compound (I) from lower cost starting materials and reagents.
It is a still further object of this invention to provide for a process to make the compound of formula (I) using safer reagents.
The present invention overcomes the problems of the reaction shown in Scheme 1 above.